This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hardwicke, M A
Right arrow Articles by Sandri-Goldin, R M
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hardwicke, M A
Right arrow Articles by Sandri-Goldin, R M

 Previous Article  |  Next Article 

J Virol. 1989 November; 63(11): 4590-4602

The regions important for the activator and repressor functions of herpes simplex virus type 1 alpha protein ICP27 map to the C-terminal half of the molecule.

M A Hardwicke, P J Vaughan, R E Sekulovich, R O'Conner and R M Sandri-Goldin

Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92717.

ABSTRACT

The herpes simplex virus type 1 (HSV-1) alpha or immediate-early proteins ICP4 (IE175), ICP0 (IE110), and ICP27 (IE63) are trans-acting proteins which affect HSV-1 gene expression. We previously showed that ICP27 in combination with ICP4 and ICP0 could act as a repressor or an activator in transfection assays, depending on the target gene (R. E. Sekulovich, K. Leary, and R. M. Sandri-Goldin, J. Virol. 62:4510-4522, 1988). To investigate the regions of the ICP27 protein which specify these functions, we constructed a series of in-frame insertion and deletion mutants in the ICP27 gene. These mutants were analyzed in transient expression assays for the ability to repress or to activate two different target genes. The target plasmids used consisted of the promoter regions from the HSV-1 beta or early gene which encodes thymidine kinase and from the beta-gamma or leaky late gene. VP5, which encodes the major capsid protein, each fused to the chloramphenicol acetyltransferase gene. Our previous studies showed that induction of pTK-CAT expression by ICP4 and ICP0 was repressed by ICP27, whereas the stimulation of pVP5-CAT expression seen with ICP4 and ICP0 was significantly increased when ICP27 was also added. In this study, a series of transfection assays was performed with each of the ICP27 mutant plasmids in combination with plasmids containing the ICP4 and ICP0 genes with each target. The results of these experiments showed that mutants containing insertions or deletions in the region from amino acids 262 to 406 in the carboxy-terminal half of the protein were unable to stimulate expression of pVP5-CAT but were able to repress induction of pTK-CAT activity by ICP4 and ICP0. Mutants in the carboxy-terminal 78 amino acids lost both activities; that is, these mutants did not show repression of pTK-CAT activity or stimulation of pVP5-CAT activity, whereas mutants in the hydrophilic amino-terminal half of ICP27 were able to perform both functions. These results show that the carboxy-terminal half of ICP27 is important for the activation and repression functions. Furthermore, the carboxy-terminal 62 amino acids are required for the repressor activity, because mutants with this region intact were able to repress. Analysis of the DNA sequence showed that there are a number of cysteine and histidine residues encoded by this region which have some similarity to zinc finger metal-binding regions found in other eucaryotic regulatory proteins. These results suggest that the structural integrity of this region is important for the function of ICP27.

J Virol. 1989 November; 63(11): 4590-4602




This article has been cited by other articles:

  • Johnson, L. A., Li, L., Sandri-Goldin, R. M. (2009). The Cellular RNA Export Receptor TAP/NXF1 Is Required for ICP27-Mediated Export of Herpes Simplex Virus 1 RNA, but the TREX Complex Adaptor Protein Aly/REF Appears To Be Dispensable. J. Virol. 83: 6335-6346 [Abstract] [Full Text]  
  • Fontaine-Rodriguez, E. C., Knipe, D. M. (2008). Herpes Simplex Virus ICP27 Increases Translation of a Subset of Viral Late mRNAs. J. Virol. 82: 3538-3545 [Abstract] [Full Text]  
  • Dai-Ju, J. Q., Li, L., Johnson, L. A., Sandri-Goldin, R. M. (2006). ICP27 Interacts with the C-Terminal Domain of RNA Polymerase II and Facilitates Its Recruitment to Herpes Simplex Virus 1 Transcription Sites, Where It Undergoes Proteasomal Degradation during Infection.. J. Virol. 80: 3567-3581 [Abstract] [Full Text]  
  • Schwartz, J. A., Brittle, E. E., Reynolds, A. E., Enquist, L. W., Silverstein, S. J. (2006). UL54-Null Pseudorabies Virus Is Attenuated in Mice but Productively Infects Cells in Culture. J. Virol. 80: 769-784 [Abstract] [Full Text]  
  • Sun, A., Devi-Rao, G. V., Rice, M. K., Gary, L. W., Bloom, D. C., Sandri-Goldin, R. M., Ghazal, P., Wagner, E. K. (2004). Immediate-Early Expression of the Herpes Simplex Virus Type 1 ICP27 Transcript Is Not Critical for Efficient Replication In Vitro or In Vivo. J. Virol. 78: 10470-10478 [Abstract] [Full Text]  
  • Ruvolo, V., Sun, L., Howard, K., Sung, S., Delecluse, H.-J., Hammerschmidt, W., Swaminathan, S. (2004). Functional Analysis of Epstein-Barr Virus SM Protein: Identification of Amino Acids Essential for Structure, Transactivation, Splicing Inhibition, and Virion Production. J. Virol. 78: 340-352 [Abstract] [Full Text]  
  • Koffa, M. D., Kean, J., Zachos, G., Rice, S. A., Clements, J. B. (2003). CK2 Protein Kinase Is Stimulated and Redistributed by Functional Herpes Simplex Virus ICP27 Protein. J. Virol. 77: 4315-4325 [Abstract] [Full Text]  
  • Lengyel, J., Guy, C., Leong, V., Borge, S., Rice, S. A. (2002). Mapping of Functional Regions in the Amino-Terminal Portion of the Herpes Simplex Virus ICP27 Regulatory Protein: Importance of the Leucine-Rich Nuclear Export Signal and RGG Box RNA-Binding Domain. J. Virol. 76: 11866-11879 [Abstract] [Full Text]  
  • Bryant, H. E., Wadd, S. E., Lamond, A. I., Silverstein, S. J., Clements, J. B. (2001). Herpes Simplex Virus IE63 (ICP27) Protein Interacts with Spliceosome-Associated Protein 145 and Inhibits Splicing prior to the First Catalytic Step. J. Virol. 75: 4376-4385 [Abstract] [Full Text]  
  • Aubert, M., Rice, S. A., Blaho, J. A. (2001). Accumulation of Herpes Simplex Virus Type 1 Early and Leaky-Late Proteins Correlates with Apoptosis Prevention in Infected Human HEp-2 Cells. J. Virol. 75: 1013-1030 [Abstract] [Full Text]  
  • Goodwin, D. J., Hall, K. T., Giles, M. S., Calderwood, M. A., Markham, A. F., Whitehouse, A. (2000). The carboxy terminus of the herpesvirus saimiri ORF 57 gene contains domains that are required for transactivation and transrepression. J. Gen. Virol. 81: 2253-2265 [Abstract] [Full Text]  
  • Ellison, K. S., Rice, S. A., Verity, R., Smiley, J. R. (2000). Processing of alpha -Globin and ICP0 mRNA in Cells Infected with Herpes Simplex Virus Type 1 ICP27 Mutants. J. Virol. 74: 7307-7319 [Abstract] [Full Text]  
  • Bunnell, S. M., Rice, S. A. (2000). The Conserved Carboxyl-Terminal Half of Herpes Simplex Virus Type 1 Regulatory Protein ICP27 Is Dispensable for Viral Growth in the Presence of Compensatory Mutations. J. Virol. 74: 7362-7374 [Abstract] [Full Text]  
  • Soliman, T. M., Silverstein, S. J. (2000). Identification of an Export Control Sequence and a Requirement for the KH Domains in ICP27 from Herpes Simplex Virus Type 1. J. Virol. 74: 7600-7609 [Abstract] [Full Text]  
  • Soliman, T. M., Silverstein, S. J. (2000). Herpesvirus mRNAs Are Sorted for Export via Crm1-Dependent and -Independent Pathways. J. Virol. 74: 2814-2825 [Abstract] [Full Text]  
  • Zhi, Y., Sandri-Goldin, R. M. (1999). Analysis of the Phosphorylation Sites of Herpes Simplex Virus Type 1 Regulatory Protein ICP27. J. Virol. 73: 3246-3257 [Abstract] [Full Text]  
  • Hann, L. E., Cook, W. J., Uprichard, S. L., Knipe, D. M., Coen, D. M. (1998). The Role of Herpes Simplex Virus ICP27 in the Regulation of UL24 Gene Expression by Differential Polyadenylation. J. Virol. 72: 7709-7714 [Abstract] [Full Text]  
  • Sandri-Goldin, R. M. (1998). ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif. Genes Dev. 12: 868-879 [Abstract] [Full Text]  
  • Sandri-Goldin, R M, Mendoza, G E (1992). A herpesvirus regulatory protein appears to act post-transcriptionally by affecting mRNA processing.. Genes Dev. 6: 848-863 [Abstract]  
  • Baudoux, L., Defechereux, P., Rentier, B., Piette, J. (2000). Gene Activation by Varicella-Zoster Virus IE4 Protein Requires Its Dimerization and Involves Both the Arginine-rich Sequence, the Central Part, and the Carboxyl-terminal Cysteine-rich Region. J. Biol. Chem. 275: 32822-32831 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»